I run a generative ruleset / code behind the screen D&D game, but I run a different one every campaign, at least so far. I look at it like how other DMs spend years improving their campaign worlds except mine is improving the game design specifically to smooth game play, cover more ground with fewer rules, increase the top challenge levels, implement ingenious strategies I've learned (usually from my players), and so on.
The campaign setting and all the elements of the setting can largely be taken from other designs like previous run campaigns though. Even the adventures can be reused, but I would need to convert them to the new campaign and system. Sometimes a lot of this comes from the players though, sometimes not. It depends on the players, but it is a good idea to have a lot of prepared material on hand so not everything needs to be remade from scratch.
Yes, I evolve mine and update it ti whatever version of the rules or houserules we are currently using. It has seen Basic, AD&D, 2nd, 3rd, 4th, FATE, Hero System, and Palladium.
"One World to rule them all, One World to find them,
One World to bring them all and in the darkness bind them".